Combined naloxone/methadone preparations for opiate substitution therapy

Loimer, Norbert; Presslich, O; Grünberger, J; Linzmayer, L

doi:10.1016/0740-5472(91)90007-w

Cited by 18 publications

(13 citation statements)

References 13 publications

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“…Increased incidence of side effects and treatment dropout have been linked with the presence of this metabolite. [36] Collaborative research between Alkemes Inc. and Cephalon Inc. led to the identification of an extended release formu- [39][40][41] Drug detoxification-Opioid abuse No Several studies have indicated that naloxone can be used effectively for the rapid detoxification of narcotic addicts [42,43] Drug-induced constipation-Opioid analgesic adverse reaction No Naloxone has been shown to be effective in treating opioid-induced constipation [44][45][46] Methadone overdose Yes Naloxone is useful in treating symptoms resulting from methadone overdose; repeated doses of naloxone may be necessary to prevent recurrence of symptoms [47,48] Opioid abuse No Naloxone therapy has been shown to be effective in the treatment of opioid-addicted patients in methadone treatment programs [49][50][51] Opioid analgesic adverse reactionRespiratory depression Yes Naloxone is indicated for the complete or partial reversal of narcotic depression including respiratory depression, induced by natural and synthetic opioids [52][53][54][55][56][57][58][59] Opioid dependence; Diagnosis No Naloxone is effective in diagnosing physical dependence in opiate addicts [60][61][62] Overdose of opiate, known or suspected; Diagnosis Yes Naloxone is indicated for the complete or partial reversal of opioid depression including respiratory depression, induced by natural and synthetic opioids [63][64][65][66][67][68] Pruritus of skin No Naloxone has been effective in narcotic-induced and cholestatic pruritus [69][70][71]…”

Section: Marketed Mu Antagonistsmentioning

confidence: 99%

Mu Opioid Receptor Antagonists: Recent Developments

2007

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For thousands of years mu opioid agonists such as morphine have been utilized for their analgesic properties. Today, morphine and related compounds are still used as a first line therapy in the treatment of moderate to severe pain. However, despite the clear benefits of mu agonists in pain management, severe side effects such as dependence and respiratory depression are associated with use of these drugs. To date, there are only two approved mu opioid antagonists for use in the treatment of these adverse effects, that is, naloxone and naltrexone. However, many other clinical and therapeutic areas have been linked to mu opioid receptor antagonism. These include treatment of opioid induced pruritis of the skin, obesity, and Parkinson‐induced tardive dyskinesia. Currently there are two compounds, N‐methylnaltrexone and alvimopan, under FDA review as possible treatments for opioid induced bowel dysfunction and postoperative ileus. These compounds are of special interest as they are peripherally restricted. This attribute enables treatment of peripheral side effects induced by opioid agonists without reversal of the centrally mediated analgesia of the agonist. In this article we discuss the structural classes of mu opioid antagonists, their potential clinical applications, and review the relevant patents of the last ten years.

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Section: Marketed Mu Antagonistsmentioning

confidence: 99%

Mu Opioid Receptor Antagonists: Recent Developments

2007

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“…A combination of oral methadone and naloxone was studied in the early 70s and 90s [30,31]. In two studies it was found that a combination of oral methadone plus naloxone could be formulated that was indistinguishable from oral methadone alone, and it has been argued that a combination of methadone and naloxone should be made available to reduce the intravenous use of methadone [31].…”

Section: Introductionmentioning

confidence: 99%

Buprenorphine and Naloxone for Heroin Dependence

Johnson

McCagh

2000

Curr Psychiatry Rep

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The pharmacology of buprenorphine is unique because of its partial agonist profile at the mu-opioid receptor (ie, high affinity, low intrinsic activity and slow dissociation). This unique profile results in greater safety, less physical dependence, and greater flexibility in dose scheduling. Buprenorphine has been investigated in combination with the opioid antagonist, naloxone, with the goal of decreasing abuse, misuse, and diversion. When combined with naloxone in a sublingual tablet, buprenorphine has been shown to be effective 1) in retaining patients in treatment, 2) in reducing opioid use and craving, and 3) when dosed less-than-daily. The pharmacologic effects of buprenorphine are not altered by the addition of naloxone when administered to the population in an appropriate combination ratio. However, if taken intravenously by individuals dependent on short- or long-acting opioids a precipitated withdrawal syndrome is observed, which should reduce its abuse potential. This review discusses the rationale for development and evidence supporting the use of a buprenorphine/naloxone combination product. The buprenorphine/naloxone combination product should be considered for use in primary care office-based settings as a safe and effective treatment that is likely to increase the availability of agonist treatment for opioid dependence.

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“…Rather, the primary emphasis has been on designing drug combinations to decrease the risk for illicit diversion of the treatment medications. For example, several investigators have examined the feasibility of combining naloxone with either buprenorphine or methadone to prevent intravenous abuse of these opioid agonist medications (Fudala et al 1998;Loimer et al 1991;Mendelson et al , 1997Mendelson et al , 1999Preston et al 1989;Weinhold et al 1992). Naloxone has poor bioavailability by oral and sublingual routes of administration and much higher bioavailability by intravenous route.…”

mentioning

confidence: 99%

Effects of Flupenthixol and Quadazocine on Self-Administration of Speedball Combinations of Cocaine and Heroin by Rhesus Monkeys

Mello

Negus

1999

Neuropsychopharmacology

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The simultaneous i.v. administration of heroin and cocaine, called "speedball," is often reported clinically, and identification of effective pharmacotherapies for polydrug abuse is a continuing challenge. This study compared the effects of treatment using combinations of dopamine and opioid antagonists with each antagonist alone onIt is increasingly recognized that drug abusers tend to use multiple drugs rather than a single drug (NIDA, 1998). Polydrug abuse often involves the concurrent abuse of cocaine and heroin, and both cocaine and continued opiate abuse have been reported in methadonemaintained patients (Condelli et al. 1991;Kosten et al. 1989b;Schottenfeld et al. 1993Schottenfeld et al. , 1997. One common form of polydrug abuse is called the speedball, which usually refers to the simultaneous intravenous administration of cocaine and heroin (NIDA, 1998;Schütz et al. 1994). Currently approved pharmacotherapies for opiate abuse have been only moderately effective in reducing polydrug abuse, and there is no consistently effective pharmacotherapy for either abuse of cocaine alone or combinations of cocaine and heroin "speedball" .Preclinical evaluation of medications for reducing Received December 10, 1998; revised March 8, 1999; accepted April 19, 1999. 576 N.K. Mello and S.S. Negus N EUROPSYCHOPHARMACOLOGY 1999 -VOL . 21 , NO . 4 polydrug abuse has been greatly facilitated by the development of animal models of speedball self-administration (Hemby et al. 1996(Hemby et al. , 1999Mello and Negus 1998;Rowlett and Woolverton 1997) and speedball discrimination (Negus et al. 1998a). Combinations of cocaine and heroin produce robust reinforcing and discriminative stimulus effects in these animal models, and cocaine and heroin may enhance each other's reinforcing and discriminative stimulus effects under some conditions (Negus et al. 1998a;Rowlett and Woolverton 1997).Similarly, neurochemical evidence suggests that selfadministration of cocaine and heroin in combination has synergistic effects on extracellular dopamine release at the nucleus accumbens in rats (Hemby et al. 1999). Dopamine levels measured by microdialysis remained at baseline levels during heroin self-administration, increased by 400% during cocaine self-administration, and increased by 1000% during speedball selfadministration, even though cocaine levels measured in dialysate samples were equivalent during cocaine and speedball self-administration (Hemby et al. 1999). Interestingly, however, the synergistic increases in dopamine levels during speedball self-administration were not accompanied by differences in operant responding maintained by cocaine and heroin alone and in combination (Hemby et al. 1999). Moreover, several other studies found that co-administration of cocaine and opioids produced discrimination stimulus and reinforcing effects that were additive or less than additive and resembled the effects of cocaine or heroin alone Negus et al. 1998b;Lamas et al. 1998;Rowlett and Spealman 1998).Taken together, these findings are cons...

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Combined naloxone/methadone preparations for opiate substitution therapy

Cited by 18 publications

References 13 publications

Mu Opioid Receptor Antagonists: Recent Developments

Mu Opioid Receptor Antagonists: Recent Developments

Buprenorphine and Naloxone for Heroin Dependence

Effects of Flupenthixol and Quadazocine on Self-Administration of Speedball Combinations of Cocaine and Heroin by Rhesus Monkeys

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